Test for Mad Cow Disease May Be Near / UCSF team bred mice to screen disorder in cattle

David Perlman, Chronicle Science Editor

Published 4:00 am, Tuesday, December 23, 1997

Laboratory mice engineered to carry genes that make them sensitive to mad cow disease could provide the first rapid test for the infection in cattle and help protect humans against a closely related brain disorder, researchers are reporting today.

At least a million cows in Britain and France have contracted the highly infectious disease, which turns their brains to spongy tissue, and infection from tainted beef is believed to have caused in more than 25 people a form of an extremely rare disorder known as Creutzfeldt-Jakob disease.

At the root of both diseases are prions, the protein particles discovered 15 years ago by Dr. Stanley B. Prusiner, a neurologist at the University of California at San Francisco who won the Nobel Prize in medicine this year for his work in the field.

The shape of the proteins can change suddenly for reasons that are still unclear, but in their distorted forms, they become the cause of severe neurological diseases in many animals, including cattle, sheep and even humans, according to the revolutionary theory first proposed by Prusiner. Today, Prusiner and his UCSF colleagues, including Dr. Steven J. DeArmond and Dr. Fred E. Cohen, report two major new findings from their work in the Proceedings of the National Academy of Sciences:

-- After six years of trial and error, they have produced "transgenic" strains of laboratory mice that carry within their cells mixtures of genes for the creation of normal prions that occur naturally in humans, cows and mice.

-- As a result, they say, they have identified a unique portion of the prion protein that allows the disease-causing form to cross the species barrier between animals and humans.

When cattle are infected with the distorted prion proteins that cause mad cow disease, Prusiner said in an interview, the symptoms do not show up for at least three to five years.

But the genetically engineered mice Prusiner and his colleagues have developed can display the staggered gait and other warning symptoms of the fatal brain disorder within 120 days, he said. By further manipulating the mice in the lab, the group expects to cut that time down to 40 days or less, Prusiner said.

Like the warnings offered by canaries in a coal mine, the mice could be inoculated with cells from symptom-free cattle and thus serve to determine whether the animals are unfit for human consumption.

Some human foods, cosmetics and drugs are made from cattle bones, and the "transgenic" mice could be used, the scientists say, to screen for the presence of the infectious prion proteins and to ensure that tainted material not be used in the manufacture of such products.

Mad cow disease, first detected in Britain in 1986, is known technically as bovine spongiform encephalitis. It is apparently caused by feed supplements contaminated with prion-infected animal protein products from diseased cattle and sheep.

Cattle in the United States are known to be free of the spongiform diseases, and the use of potentially contaminated animal- based feed is banned. No cases of Creutzfeldt-Jakob disease attributable to infection from diseased animals have occurred in this country, according to public health experts at the U.S. Centers for Disease Control.

Prusiner and his group are now trying to determine how normal prions -- which are found in all human and animal tissues -- can become transformed into highly infectious disease-causing agents.

The answer, Prusiner believes, is a mysterious "Factor X," a protein molecule that binds with a normal prion and distorts its shape. But he expects extensive research will be needed to identify the molecule and how it works. "It's not an easy secret to extract from nature," he said.

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